Bacteriostat and fungistat compositions containing n,s-heterocyclic compounds

ABSTRACT

The use of Delta 2-thiazolines and 4,5-dihydro-1,3-thiazines as bacteriostats and fungistats. Used alone or with a carrier, they are effective in inhibiting the growth of bacteria and fungi. The N,S-heterocyclics are especially effective against gram-positive bacteria.

limited States Patent Junghahnel et al.

[ 51 Aug. 1, 1972 [54] BACTERIOSTAT AND FUNGHSTAT COOSlTlONS CONTAININGN,S- HETEROCYCLIC CONWOUNDS [72] Inventors: Rudolph Junghahnel,Witten-Bommern; Gustav Renckhoff, Witten- Ruhr; Klaus Thewalt,Witten-Ruhr,

all of Germany [73] Assignee: Dynamit Nobel Aktiengesellschaft,

Troisdorf, Germany [22] Filed: July 16,1968

[21] Appl. No.: 745,087

UNITED STATES PATENTS 3,471,618 10/1969 Beereboom ..424/246 OTHERPUBLICATIONS Wenker, J. Am. Chem. Soc., Vol. 57, p. 1029- 80 (1935)Sheehan et al., J. Am. Chem. Soc., Vol. 23, p. 4367 72 (1951) Iwakura etaL, J. Org. Chem, Vol. 31, p. 3352- 56 Primary Examiner-Albert T. MeyersAssistant ExaminerVincent D. Turner Attorney-Craig, Antonelli & Hill 57I ABSTRACT The use of A -thiazolines and 4,5-dihydro-l ,3- thiazines asbacteriostats and fungistats. Used alone or with a carrier, they areeffective in inhibiting the growth of bacteria and fungi. TheN,S-heterocyclics are especially effective against gram-positivebacteria.

7 Claims, No Drawings BACTERIOSTAT AND FUNGISTAT COMPOSITIONS CONTAININGN,S- HETEROCYCLIC COMPOUNDS BACKGROUND OF THE INVENTION The presentinvention relates to the utilization of novel cyclic N-S compounds asbacteriostats and fungistats. More particularly, it relates to A-thiazolines and 4,5-dihydro-l,3-thiazines and to their use ininhibiting the growth of bacteria and fungi.

N-S-heterocyclic compounds have been examined in a plurality of caseswith respect to their bacteriostatic and fungistatic properties.However, in this regard, there is no prior art teaching the use of A-thiazolines and 1,3-thiazines.

SUMMARY OF THE INVENTION One of the objects of the present invention isto provide novel bacteriostat and fungistat compositions.

Another object of the present invention is to provide a process foreffectively inhibiting the growth of bacteria and fungi in a relativelysimple and direct manner.

A further object of the invention is to effectively use the desirablebacteriostat and fungistat properties possessed by A -thiazolines and1,3-thiazines.

These and other objects and advantages of the present invention willbecome apparent to those skilled in the art from a consideration of thefollowing specification and claims.

In accordance with the present invention, it has been found that A-thiazolines and 4,5-dihydro-l ,3-thiazines having the general formula:

wherein R is a branchedor straight-chain aliphatic group of five to 12carbon atoms, in particular C C alkyl, R, is methyl or hydrogen and n isl or 2, exhibit a good bacteriostatic and fungistatic effect withrespect to gram-positive and gram-negative bacteria, as well as againstvarious genera of fungi.

The compounds with h=2, utilized in the present invention can beprepared, for example, in accordance with the disclosure in copendingapplication Ser. No. 728,075 filed on May 9, 1968 (now US Pat. No.3,528,973) the disclosure of which is herein expressly incorporated byreference. Briefly, these 1,3-N-S- heterocyclic compounds are preparedby reacting hydroxyalkyl amides of the general formula, RCONHCH -(CH),,CH OH, with phosphorus pentasulfide.

The tests showing the effectiveness of the compounds utilized in thepresent invention were conducted in accordance with the followingmethods:

1. The detection of bacteriostatic and fungistatic effects waseffectuated with the aid of the dilution test along the lines of theregulations promulgated by the Deutsche Gesellschaft fur Hygiene andMikrobiologie (German Society for Hygiene and Microbiology), for thetesting of chemical disinfectants.

2. The growth test was conducted in accordance with DIN PreliminaryStandard 53,931.

The effectiveness of the N-S-heterocyclics against gram positivebacteria (Staphylococcus Aureu.r)is stronger than that againstgram-negative ones (Bacterium coli). The efiective concentration againstgrampositive bacteria is below 0.012 percent by weight in the case of:

2-heptyl-dihydro-6I-ll ,3-thiazine 2-octyl-dihydro-6H- l ,3-thiazine2-hexyl-dihydro-6H- l ,3-thiazine Z-(Q; C )-4,5-dihydro-6H-l,3-thiazine, and below 0.06 percent by weight in the case of:

2-heptyl-thiazoline-2 2-nonyl-thiazoline-2.

Against gram-negative bacteria, the inhibitory effect is below 0.06percent in the case of the following compounds:

2-heptyl-dihydro-6I-ll ,3-thiazine 2- -octyl-dihydro-6H- l ,3-thiazine.

Against molds (Aspergillus niger), inhibitory concentrations of below0.06 percent are found in the case of the following compounds:

2-nonyl-dihydro-6H- 1 ,3-thiazine 2-octyl-dihydro-6I-I- l ,3-thiazine.

A 4 percent coating of the following compounds on nettle fabric provedto be an effective growth inhibitor against mold fungus (Aspergillusniger):

2-nonyl-dihydro-6l-ll ,3-thiazine 2-undecanoyl-4,5-dihydro-6H- l,3-thiazine 2-(C C )-4,5-dihydro-6H- l ,3-thiazine.

It is to be understood that the above specific examples are given merelyas illustrative of the present invention and are not to be considered aslimiting. Unless otherwise noted, the percentages are by weight.

It is also to be understood that not all of the compounds utilized inthe process of the present invention are effective to the same degree.However, one skilled in the art should be able to ascertain an effectiveconcentration which would be warranted in any given situation.

The compounds employed in the invention may be used either per se or asa composition together with a suitable inert carrier. A typicalinertcarrier which may be utilized is, for example, an inert hydrocarbonsolvent, such as toluene or xylene.

The invention being thus described, it will be obvious that the same maybe varied in many ways. Such variations are not to be regarded as adeparture from the spirit and scope of the invention, and all suchmodifications are intended to be included within the scope of thefollowing claims.

We claim:

1. A process for inhibiting the growth of microorganisms selected fromthe group consisting of bacteria and fungi which comprises applying tosaid microorganisms a growth-inhibiting amount of a cyclicN,S-heterocyclic compound having the formula:

wherein R is a branchedor straight-chain aliphatic 3. The process ofclaim 1, wherein said microorganisms are gram-negative bacteria and saidcompound is selected from the group consisting of Z-heptyl-dihydro- 6H-l,3-thiazine, and 2-octyl-dihydro-6H- l ,3 -thiazine.

4. The process of claim 1, wherein said microorganisms are molds andsaid compound is selected from the group consisting of2-nonyl-dihydro-6H-i,3-thiazine, 2-octyl-dihydro-6H- l ,3-thiazine,2-undecanoyl-4,5- dihydro-6H-1,3-thiazine and 2-(C C, )-4,5- dihydro-6H-1 ,3-thiazine.

5. A process for inhibiting the growth of bacteria and fungi whichcomprises treating a nettle fabric with a growth-inhibiting amount of anN,S-heterocyclic compound having the formula:

2)n R-L HRl s wherein R is a branchedor straight-chain aliphatic groupof five to 12 carbon atoms, R is methyl or hydrogen and n is l or 2.

6. A bacteriostat and fungistat composition comprising an effectivebacteriostatic or fungistatic amount of a cyclic N,S-heterocycliccompound having the formula:

N crn 11- (EHRI wherein R is a branchedor straight-chain aliphatic groupof five to 12 carbon atoms, R is methyl or hydrogen and n is 1 or 2, andan inert hydrocarbon solvent.

7. The composition of claim 6, wherein said inert carrier is toluene orxylene.

2. The process of claim 1, wherein said microorganisms are gram-positivebacteria and said compound is selected from the group consisting of2-heptyl-dihydro-6H-1,3-thiazine, 2-octyl-dihydro-6H-1,3-thiazine,2-hexyl-dihydro-6H-1,3-thiazine, 2-(C6-C12)-4,5-dihydro-6H-1,3-thiazine,2-heptyl-thiazoline-2 and 2-nonyl-thiazoline-2.
 3. The process of claim1, wherein said microorganisms are gram-negative bacteria and saidcompound is selected from the group consisting of2-heptyl-dihydro-6H-1,3-thiazine, and 2-octyl-dihydro-6H-1,3-thiazine.4. The process of claim 1, wherein said microorganisms are molds andsaid compound is selected from the group consisting of2-nonyl-dihydro-6H-1,3-thiazine, 2-octyl-dihydro-6H-1,3-thiazine,2-undecanoyl-4,5-dihydro-6H-1,3-thiazine and 2-(C6 -C12)-4,5-dihydro-6H-1,3-thiazine.
 5. A process for inhibiting the growthof bacteria and fungi which comprises treating a nettle fabric with agrowth-inhibiting amount of an N,S-heterocyclic compound having theformula: wherein R is a branched- or straight-chain aliphatic group offive to 12 carbon atoms, R1 is methyl or hydrogen and n is 1 or
 2. 6. Abacteriostat and fungistat composition comprising an effectivebacteriostatic or fungistatic amount of a cyclic N,S-heterocycliccompound having the formula: wherein R is a branched- or straight-chainaliphatic group of five to 12 carbon atoms, R1 is methyl or hydrogen andn is 1 or 2, and an inert hydrocarbon solvent.
 7. The composition ofclaim 6, wherein said inert carrier is toluene or xylene.